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Activation of microglia with lipopolysaccharide leads to the prolonged decrease of conventional protein kinase C
Kazuyuki Nakajima1, Shinichi Kohsaka, Yoko Tohyama
1Neurochemistry Division, Institute of Life Science, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan. nakajima@t.soka.ac.jp
Brain Research. Molecular Brain Research
|February 8, 2003
Summary
Lipopolysaccharide (LPS) activates microglia, producing harmful factors. This study shows that while LPS decreases conventional protein kinase C (PKC) activity, a residual amount is sufficient for sustained microglial activation.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial activation by lipopolysaccharide (LPS) leads to the release of detrimental factors like nitric oxide and tumor necrosis factor alpha (TNFalpha).
- Previous studies suggested a role for protein kinase C (PKC) in mediating microglial activation, based on inhibitor experiments.
Purpose of the Study:
- To elucidate the precise relationship between microglial activation and conventional PKC (cPKC) activity.
- To investigate the role of cPKC in the induction of harmful factors by LPS-stimulated microglia.
Main Methods:
- Measurement of cPKC activity in LPS-activated microglia using enzyme-linked immunosorbent assay (ELISA).
- Quantification of PKCalpha levels to understand changes in cPKC activity.
Main Results:
- LPS stimulation resulted in a significant, time- and dose-dependent decrease (up to 70%) in cPKC specific activity.
- The reduction in cPKC activity was primarily attributed to decreased levels of PKCalpha.
- A sustained level of approximately 30% of the original cPKC activity remained, even with prolonged LPS exposure or higher concentrations.
Conclusions:
- LPS-stimulated microglia appear to require an initial PKC activation 'priming' phase for the subsequent induction of harmful factors.
- A partial, sustained PKC activity (around 30%) is sufficient to maintain microglial activation.
- These findings suggest a complex, biphasic role for PKC in regulating microglial inflammatory responses.